tbuckley/cabot-search huggingface dataset:
Body Temperature Enhanced Adhesive, Antibacterial, and Recyclable Ionic Hydrogel for Epidermal Electrophysiological Monitoring
Authors: Ying Liu, Chan Wang, Jiangtao Xue, Guanhua Huang, Shuang Zheng, Ke Zhao, Jing Huang, Yiqian Wang, Yan Zhang, Tailang Yin, Zhou Li
Journal: Advanced Healthcare Materials (2022)

Hydrogel-based epidermal electrodes attract widespread attention in health monitoring and human-machine interfaces for their good biocompatibility, skin-matched Young's modulus, and stable in situ electrophysiological recording performance. However, it is difficult to make the exact conformal attachment between skin and electrodes because of the hair, wrinkles, as well as complex, curved contours of the skin. This also results in signal distortion and large noise. Here, a body temperature enhanced skin-adhesive epidermal electrode is proposed based on non-covalent cross-linked network ionic hydrogel. The ionic hydrogel is fabricated by the polyvinyl alcohol, branched polyethyleneimine, and calcium chloride (CaCl2 ), which demonstrates impressive performances including ultra-stretchability of 1291%, great adhesion to skin and other non-biological materials, stable conductivity of 3.09 S m-1 , recyclability, and outstanding antibacterial ability, simultaneously. Specifically, the adhesion of the ionic hydrogel behaves as temperature-sensitive and could be enhanced by body temperature. Furthermore, the ionic hydrogel is utilized as epidermal electrodes, which display seductive capability to record multifarious electrophysiological signals with high signal-to-noise ratio and ultra-low detection limit, including electrocardiogram, electromyogram, and electroencephalogram. The as-proposed body temperature enhanced skin-adhesive ionic hydrogel brings intelligent functions and broadens the way for epidermal electronics, promoting the development of healthcare electronics.
The impact of COVID-19 on patients with cancer in the Oncology Care Model in the U.S. Oncology Network during performance period 8.
Authors: Lalan S. Wilfong, Hope Ives, Puneeth Indurlal, Stuart Staggs, Judi Payne-De Bock, Marcus A. Neubauer
Journal: Journal of Clinical Oncology (2022)

e18747 Background: The COVID-19 pandemic had a profound impact on cancer care delivery throughout the nation. Data regarding the outcomes of patients on cancer therapy who had COVID-19 is lacking. The US Oncology Network had 14 practices participating in the Oncology Care Model (OCM) during performance period 8 (PP8) which enrolled patients from 1/2/2020 to 7/1/2020. OCM enrolls patients with Medicare undergoing treatment for a cancer diagnosis. Utilizing OCM claims files, we evaluated the impact of COVID-19 on outcomes and costs for patients enrolled in the OCM during the first stages of the pandemic. Methods: Utilizing claims and episode data from the OCM, we were able to identify episodes with patients who had a positive COVID-19 diagnosis. Episodes were flagged with COVID-19 based on the ICD-10 code U07.1 on claims files. We were then able to compare the total cost of care (TCOC), inpatient costs and death rate to those patients in the OCM that did not have a COVID-19 ICD-10 claim. Results: 2.5% of patient episodes in PP8 had a positive COVID-19 ICD-10 claim. TCOC per episode increased 36% per patient from $34,340 for those without COVID-19 to $53,605 for those with COVID-19, a difference of $19,265 per patient. Inpatient costs increased from $3,276 for those without COVID-19 to $12,226 for those with a COVID-19 diagnosis. 8.9% of patients without a COVID-19 diagnosis died during the episode vs 20.0% of those with a COVID-19 diagnosis. Other costs including the cost of drugs did not significantly differ between the two groups. Conclusions: A diagnosis of COVID-19 for patients in the OCM receiving cancer treatment during PP8 led to a significant increase in costs, especially the costs of hospitalization. The death rate more than doubled for patients with COVID-19 during an OCM episode. Patients with Medicare and cancer undergoing treatment were at high-risk for complications and death from COVID-19 during OCM performance period 8.
MEDB-83. A novel epigenetic nanotherapeutic strategy to induce medulloblastoma differentiation
Authors: Praveen Raju, Daniel Tylawsky, Jake Vaynshteyn, Jeffrey Gerwin, Daniel Heller, Matija Snuderl
Journal: Neuro-Oncology (2022)

Abstract The histone-lysine N-methyltransferase EZH2 is the catalytic component of the PRC2 complex and is overexpressed in several medulloblastoma subtypes. However, its role in medulloblastoma tumorigenesis has been shown to be context-dependent using genetic approaches. Furthermore, pharmacological approaches have been limited by the very poor blood-brain barrier (BBB) penetration of current EZH2 inhibitors in use. Using laser capture microdissection and RNA-Seq analysis of human nodular/desmoplastic SHH medulloblastoma FFPE tissue, we provide data for the spatial epigenetic heterogeneity of primitive/proliferative regions compared to nodular/mature regions. Bioinformatic analysis identifies ~120 differentially expressed genes between primitive and mature regions with enrichment for genes regulated by H3K4me3 and H3K27me3 or SUZ12. ChIP-Seq analysis shows striking differences in H3K27me3 enrichment between primitive and mature medulloblastoma cells including at the EZH2 locus. Utilizing a genetically-engineered mouse model of SHH medulloblastoma, we show that conditional EZH2 genetic ablation within medulloblastoma cells results in wide-spread tumor cell differentiation (n=31 mice; *p=2e-07). Conversely, conditional EZH2 (Y641F) activation in this GEM model prevents tumor cell differentiation. Notably, we have found that the CDNK2A (p16) locus is an important EZH2 target that regulates tumor cell differentiation. qRT-PCR analysis of SHH medulloblastoma in wild-type and Ezh2 knockout settings show significant reduction in Gli1 and CCND1 and increase p15 and p16 expression in Ezh2 knockout mice compared to Ezh2 wildtype mice (*p&amp;lt;0.05). Importantly, genetic ablation of p16 conditionally in SHH MB EZH2 double knockout mice rescues the widespread tumor cell differentiation (n=9 mice; *p=3e-06) seen in Ezh2 single knockout SHH medulloblastoma mice. Finally, we developed a novel fucoidan-based nanoparticle strategy to deliver the EZH2 inhibitor (EPZ-6438) across the intact BBB of this GEM model to achieve significant extension of mouse survival (median 70 days compared to 19 days in control mice; *p=0.01, Mantel-Cox) with potential utility for other pediatric brain tumors.
De-escalation of chemotherapy in elderly women using a 70-gene platform: Comparison of the MINDACT study with a real-world study in the Brazilian population (AGEMA-BRA).
Authors: Fabio Mansani, Vitória Celinski, Ruffo Freitas-Junior
Journal: Journal of Clinical Oncology (2022)

e12568 Background: The application of genetic signatures can contributes to determine a less toxic treatment in ederly women with luminal biological profile tumors, where toxicity is less tolerated and with a higher risk of fatal outcomes by therapy. The MINDACT study evaluated this population using MammaPrint, but patients over 70 years of age were poorly represented, corresponding only to 0.8% of the patients evaluated (56 of 6693 patients), and only 26 patients with high clinical risk. Objective: The aim of this study was to verify the possibility of de-escalation of systemic treatment with the use of MammaPrint genetic signature in elderly women, comparing the prevalence of data from the MINDACT study population with a cohort of Brazilian patients submitted to the examination (AGEMA-BRA). Methods: Cross-sectional study comparing the prevalence of low and high risk genomic patients in a population with luminal profile breast carcinoma with high clinical risk in MINDACT study populations with a Brazilian cohort older than 70 years, evaluated by the genetic signature MammaPrint, between 2016 and 2020. Descriptive analysis of data with estimation of simple and relative frequencies of variables in relation to low and high risk classification and study populations (AGEMA-BRA and MINDACT). Then, the chi-square test was used to verify the differences between the proportions. To measure the intensity of differences/associations, relative risks (RR) and their 95% confidence intervals (95% CI) were calculated. The tests were considered significant when p &lt;0.05. Results: From a database of 950 patients submitted to MammaPrint analysis from 2016 to 2020. The population older than 70 yo (71-84 yo) at the time of diagnosis was represented by 89 patients (9.4%), all with high clinical risk. Of these patients, 54 (60.7%) corresponded to low genomic risk and 35 (39.3%) at high genomic risk. The comparative analysis between the prevalence of the Brazilian population and the MINDACT study, in which the low genomic risk was 61.5% and the high genomic risk 38.5%, showed no statistical significance (RR 0.98 (0.69-1.39) p= 0.936). Conclusions: The comparative analysis of the prevalence among the results of MammaPrint in the MINDACT study and in a cohort of Brazilian women (AGEMA-BRA) in the population older than 70 years, showed no statistical difference. With the confirmation of MINDACT data in this age group in a three-fold larger cohort (AGEMA-BRA), it is inferable that, although the low representativeness in the studies, the genetic signature MammaPrint can be applied in the elderly woman. Evaluation of outcomes regarding relapse-free survival and overall survival, an ongoing study, is necessary to confirm the data obtained.
Single institution assessment of compliance with guideline directed aspirin therapy in the prevention of colorectal cancer in Lynch syndrome.
Authors: Kathie Wu, Heinric Williams, Nadia N. Ramdin
Journal: Journal of Clinical Oncology (2022)

e13637 Background: Patients with Lynch syndrome have up to 80% lifetime risk of developing colorectal cancer. Research shows chemoprevention with aspirin 600 mg for 25 months can reduce this risk for Lynch syndrome patients by 59%. In our study, we evaluated the compliance with aspirin therapy among Lynch patients at our institution. Methods: Our clinic identifies and follows all patients with a history of Lynch syndrome. Of our 125 patients, 62% were discovered after a family member was found to have a high-risk cancer, 29% were identified through MyCode, a DNA sequencing program which looks for gene mutations specific to Lynch. All patients in the clinic undergo discussion about starting aspirin therapy. Medication agreements and dosing are documented in the chart. Data was retrospectively reviewed to assess our patient compliance with recommendations. All data was based on subjective reports of compliance and reported doses. Results: 125 patients were included in the data analysis. Various risk factors were assessed including age, gender, history of cancer, and other comorbidities. Ages ranged from 20 to 78; 74% were female, 26% male. 90% of patients had a family cancer and of those, 47% had a personal history of cancer. Overall, 57% of patients agreed to take aspirin with doses ranging between 81 mg to 600 mg. 60.8% of patients took 81 mg of aspirin daily and 30.6% took 325 mg daily, citing concerns for bleeding and ulcer at higher doses. Only 8% of all patients agreeable to aspirin therapy took the recommended 600 mg dose. Of those who refused aspirin therapy, 5% reported allergy or prior intolerance, 13% had history of gastric ulcer or prior bleeding, 2% were taking medications which taken concomitantly with aspirin would increase risk of bleeding, and 80% provided no reason. Chi square test of independence was performed to examine the relationship between aspirin use and gender (χ² = 0.76, p = 0.38), age (χ² = 1.99, p = 0.37), and personal or family history of cancer (χ² = 9.89, p = .002). Results showed a patient with personal, or family history of cancer was more likely to take aspirin therapy, but there was no significant relationship among gender or age. Conclusions: Aspirin serves as an effective and affordable therapy for the prevention of colorectal cancer in patients with Lynch syndrome. Barriers to compliance should be identified and chemoprophylaxis should be initiated in all qualified patients. Future studies should be performed to establish more concrete recommendations about dosing and duration of aspirin therapy especially given the ease of access and cost effectiveness.[Table: see text]
Aquablation in very large prostates (&gt;150mL): Technique and multicenter case series
Authors: A. Glaser, B. Helfand, A. Kasraeian, S. Sterious, P. Talaty, M. Alcantara, K. Alcantara, A. Higgins, E. Ghiraldi, D. Elterman
Journal: European Urology (2022)
Impact of non-muscle invasive bladder cancer treatment history on the efficacy of pembrolizumab for patients with metastatic urothelial carcinoma
Authors: R. Taoka, T. Kobayashi, Y. Hidaka, H. Abe, S. Morita, O. Ogawa, H. Nishiyama, H. Kitamura, M. Sugimoto
Journal: European Urology (2022)
Olanzapine versus fosaprepitant for prevention of chemotherapy induced nausea and vomiting in patients receiving carboplatin (AUC ≥ 4) containing chemotherapy regimen: A phase 3 randomized, double-blind, placebo-controlled trial.
Authors: Sneh Bhargave, akash kumar, Vinod Sharma, Babita Kataria, Deepam Pushpam, Atul Batra, Raja Pramanik, Sachin Khurana, Ranjit Kumar Sahoo, Prabhat Singh Malik, Sameer Bakhshi, Atul Sharma, Lalit Kumar
Journal: Journal of Clinical Oncology (2022)

TPS12149 Background: Chemotherapy-induced nausea and vomiting (CINV) is a common adverse effect affecting quality of life of patients of cancer undergoing chemotherapy. Carboplatin alone or in combination with various other chemotherapy drugs is one of the most commonly used drug in solid malignancies. It is categorised as a highly emetogenic drug in doses above AUC≥4 and multiple past studies revealed high CINV incidence. Current international antiemetic guidelines suggest NK1 receptor antagonist based triplet drugs as an effective regimen of CINV control in these patients. However, the nausea control rates are largely inadequate. Olanzapine, an atypical antipsychotic drug, is another drug that has shown significant activity in CINV control and is an integral part of current chemotherapy induced emesis and nausea prevention. However, robust comparative studies of olanzapine based triplets with NK1 based combination have been lacking. Hence we planned this study to compare efficacy of olanzapine containing triplet with NK1 receptor antagonist (fosaprepitant) based triplet drug combination in a phase 3 randomised study. Methods: This study is an investigator initiated phase 3 prospective randomised double blind placebo controlled trial comparing efficacy of olanzapine, 5HT3 receptor antagonist(ondansetron) and dexamethasone (experimental arm) against fosaprepitant, 5HT3 receptor antagonist(ondansetron) and dexamethasone (standard arm) for prevention of CINV among chemo-naïve patients (aged ≥18 years) receiving carboplatin (AUC ≥4) based chemotherapy regimen. Primary objective is to compare the number of patients with no nausea during overall periods (0-120 hours post-chemotherapy). Secondary objectives are to compare complete response (no emetic episodes and no use of rescue medication) in the acute(0-24 hr), delayed(25-120 hr),overall periods(0-120 hr) and to assess the frequency of rescue medication use. The other secondary objective includes assessment of adverse events in both the arms. Statistical Design: Planned accrual is total 214 patients including 10% drop out rate. It is a superiority design with an absolute improvement of 20% in the proportion of patients with no nausea from a baseline prevalence of 40% in the standard arm and two sided alpha of 5% as well as power of 80%. Conduct to date :Study activation : March 2021. Enrolment : 138 subjects. Clinical trial information: CTRI/2021/03/032165.
Phase 1b/2 study of ladiratuzumab vedotin (LV) in combination with pembrolizumab for first-line treatment of triple-negative breast cancer (SGNLVA-002, trial in progress).
Authors: Jane Lowe Meisel, Timothy J. Pluard, Shaveta Vinayak, Erica Michelle Stringer-Reasor, Ursa Brown-Glaberman, Patrick Michael Dillon, Reva K Basho, Ramya Varadarajan, Joyce O'Shaughnessy, Hyo S. Han, Rajni Sinha, Jenny R. Fox, Rafael Villanueva, Lin Chi Chen, Sheng Wu, Hong Li, Sinhan Tran, Luis Manso
Journal: Journal of Clinical Oncology (2022)

TPS1127 Background: Patients with metastatic triple-negative breast cancer (mTNBC) have a poor prognosis. Treatment combinations of anti-programmed death ligand 1 (anti–PD-L1) agents with chemotherapy have shown promise in mTNBC. LV is an investigational antibody–drug conjugate directed to LIV-1, a protein highly expressed on breast cancer cells, via a humanized IgG1 monoclonal antibody conjugated to monomethyl auristatin E (MMAE) by a protease-cleavable linker. LIV-1–mediated delivery of MMAE disrupts microtubules and induces cell cycle arrest and apoptosis. LV has also been shown to drive immunogenic cell death (ICD) to elicit an immune response. LV + pembrolizumab may result in synergistic activity through LV-induced ICD, creating a microenvironment favorable for enhanced anti–PD-L1 activity. Preliminary results show LV delivered once every 3 weeks (Q3W) + pembrolizumab was tolerable with encouraging antitumor activity in patients with mTNBC (Han 2019). Additionally, interim results of weekly LV monotherapy at doses up to 1.5 mg/kg were clinically active and generally well tolerated (Tsai 2021). Based on pharmacokinetic and pharmacodynamic modeling and simulation analysis, an intermittent LV + pembrolizumab dosing regimen is being evaluated to further enhance efficacy and improve the tolerability profile. Due to an unmet medical need for patients with mTNBC who are PD-L1 low or negative, Part D will focus on this patient population. Methods: SGNLVA-002 (NCT03310957) is an ongoing global single-arm, open-label phase 1b/2 study of LV + pembrolizumab as 1L therapy for patients with unresectable locally advanced/mTNBC. Part D is currently enrolling ̃40 patients. Eligible patients must have advanced disease with no prior cytotoxic/anti–PD-L1 treatment, PD-L1 combined positive score &lt; 10, measurable disease per RECIST v1.1 and an ECOG score ≤1. Patients with Grade ≥2 pre-existing neuropathy or active central nervous system metastases are not permitted. Patients will receive LV at 1.5 mg/kg on Days 1 and 8 plus pembrolizumab 200 mg on Day 1 Q3W. The primary objectives are to evaluate the safety/tolerability and objective response rate of LV + pembrolizumab. Secondary objectives include duration of response, disease control rate, progression-free survival, and overall survival. Safety and efficacy endpoints will be summarized with descriptive statistics. Global enrollment is ongoing in the US, EU, and Asia. Clinical trial information: NCT03310957.
Covid-19 vaccine in prison: a not-to-be-missed opportunity to promote access to vaccination in adolescents
Authors: Sara Mazzilli, Babak Moazen, Heino Stover, Emma Plugge, Lara Tavoschi
Journal: BMJ (2022)

Covid-19 vaccination campaigns for adolescents have been taking place in many countries for some months. 1 2 The WHO Strategic Advisory Group of Experts on immunisation have called for vaccine prioritisation within countries to take into account the needs of those groups that, due to underlying social, ethnic, geographic, or biomedical factors, are at greater risk of getting infected or suffering most severe consequences from covid-19. 3 Since the risk of transmission of SARS-CoV-2 is considerably higher in prisons and detention facilities than elsewhere, adolescents who are detained in juvenile institutions should be prioritised for vaccination.
HGG-26. Comprehensive Genomic Profiling of Pediatric and AYA High-Grade Gliomas Reveals a High Prevalence of ATRX and Homologous Recombination Repair (HRR) Mutations
Authors: Zheng Kuang, Matthew Hiemenz, Michael Angelo Huang
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Pediatric high-grade glioma (HGG) is a devastating heterogenous disease with a clear need for more effective treatment options. Advances in high-throughput molecular sequencing have advanced our understanding of these tumors and yet outcomes remain poor as only a very small subset of patients have demonstrated benefit from targeted therapy approaches. METHODS: We compiled genomic data from 980 pediatric (N=400) and AYA (18 to 30 yrs, N=580) HGG cases that underwent targeted, panel-based comprehensive genomic profiling (FoundationOne® CDx). RESULTS: Among pediatric patients, mutations in ATRX or HRR-related genes were among the most prevalent at 24.25% and 19.5%, respectively. Other commonly occurring mutations were seen in TP53 (58.25%), H3F3A (43%), and PIK3CA/PIK3R1 (22%). Among AYA patients, mutations in ATRX and HRR-related genes were seen in 51.72% and 17.24% of cases, respectively. The most common mutations seen in this older population were in TP53 (76.38%), IDH1/2 (50.86%), PI3KCA/PIK3R1 (20.52%), and H3F3A (18.28%). Among patients with diffuse midline glioma (harboring H3K27M mutations), ATRX and HRR mutations were reported in 21.27% and 13.57% of cases, respectively. Among pediatric patients with histone wild type HGG, mutations in ATRX and HRR-related genes occurred in 20.61% and 21.05% of cases, respectively. CONCLUSION: Alterations in ATRX and HRR-related genes are among the most prevalent mutations in pediatric and AYA HGG. Consideration should be made towards the development of subtype-specific treatment protocols using PARP and/or ATR inhibitors aimed at this subgroup of patients.
MEDB-54. Standard Risk Medulloblastoma treated solely with surgery and chemo-radiation
Authors: Evan Cantor, Ashley Meyer, Andrea Ogle, Michele McHugh, Mary Beck, Tammy Green, Lakshmi Ramachandran, Sonika Dahiya, Andrew Cluster, Nicole M Brossier, Mohamed S Abdelbaki, David Limbrick, Stephanie Perkins, Margaret Shatara
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Medulloblastoma is the most common malignant brain tumor in children, with 5-year overall survival (OS) ranging from 60%-95% depending on subgroup and risk status. The POG 8631/CCG 923 trial (accrual 1986-1990) found a 63% 5 year OS for patients with local disease after gross total resection treated with radiation at a dose of 23.4 Gy craniospinal radiation and posterior fossa boost to 54 Gy, vs. 80.5% 5-year OS for patients treated as per full ACNS0331 therapy including maintenance chemotherapy. Herein, we describe a long-term survival with standard-risk medulloblastoma who only received surgical resection and radiation therapy. CASE: A 17-year-old male presented with acute onset of hypertension, bradycardia, headache, and blurry vision and was found to have a heterogeneously enhancing posterior fossa mass with mass effect on the fourth ventricle and hydrocephalus on brain MRI. He underwent gross total resection of the tumor and histopathology revealed medulloblastoma with classic and large cell features. Fluorescence in situ hybridization (FISH) was negative for MYC, MYCN amplification, or HER2 gain. Cerebrospinal fluid cytology was negative for neoplastic cells, and spinal MRI did not reveal any drop metastases. The patient initiated therapy per ACNS0331 with craniospinal irradiation posterior fossa boost. He also received weekly vincristine. After completion of radiation therapy, the family declined further chemotherapy despite medical advice. He had no evidence of relapse most recently at 51 months from completion of therapy. Next generation sequencing and methylation testing are currently pending. CONCLUSION: Current efforts aim at optimizing therapy based on molecular subgrouping, to minimize long-term adverse events associated with current therapies. We report a unique case of an adolescent male with an standard-risk medulloblastoma, who achieved remission with only radiotherapy. Further molecular tumor analysis may elucidate the response of the tumor.